Fentanyl and fentanyl citrate are synthetic narcotic analgesics which have been confirmed being about 200 times more potent in analgesic activity than morphine in animal experiments. Nowadays fentanyl-containing reservoir-type long-acting preparations of the percutaneous absorption type are commercially available for relieving cancer-caused pains and, with such preparations, the blood concentration of fentanyl can be maintained practically at effective levels for 24 to 72 hours.
However, such reservoir-type long-acting preparations of the percutaneous absorption type are disadvantageous in that the drug absorption after application thereof is fairly slow and the blood concentration arrives at an effective level only after 12 to 24 hours following the initial application, so that they cannot produce an immediate analgesic effect, in that because of their being reservoir-type preparations, they have the problem of fluid leakage, and in that they are very strong irritant to the lesion of application due to their containing ethanol.
Attempts have so far been made to produce matrix-type patches for percutaneous absorption as means for solving the above problems. For example, preparations for percutaneous absorption in which an acrylic adhesive is used as a main base are proposed in Patent Documents 1 and 2. However, the acrylic adhesive is generally inferior in drug-release, causing a problem: namely, a desired level of drug-release can be attained only by increasing the content of a main drug. The increase in the main drug content causes other problems, for example the problem of crystallization of the main drug during storage, and the problem of residual fentanyl in the preparation after application thereof. Preparations comprising polyisobutylene as the main base have also been disclosed in Patent Documents 3 and 4.
On the other hand, while fentanyl-containing patches in which a styrene-isoprene-styrene block copolymer (hereinafter abbreviated as “SIS”) is used as a main base (SIS-based preparations) have also been disclosed in Patent Documents 5 and 6, there have not yet been developed any patches capable of simultaneously guaranteeing prolonged stable main drug-release on the occasion of use, long-term storage stability and safety to the skin during prolonged application thereto. It has been shown that N-methyl-2-pyrrolidone, for instance, used as an absorption enhancer in a SIS-based preparation has the effect of reducing the period of delay in percutaneous absorption owing to the absorption promoting action of N-methyl-2-pyrrolidone; since, however, N-methyl-2-pyrrolidone is volatile, there arises a problem: namely, N-methyl-2-pyrrolidone may evaporate during storage and/or application, possibly resulting in changes in drug-release (Patent Document 5). Furthermore, a patch for percutaneous administration of fentanyl or an analog thereof has been proposed in Patent Document 7. While this art, too, relates to a matrix type preparation which comprises a monolayer polymer phase, the preparation is characterized in that it is biologically equivalent to the commercially available fentanyl preparations mentioned above; therefore, as regards the time course of the blood concentration of fentanyl following administration, the preparation still has the drawback that it fails to produce an immediate analgesic effect, like the reservoir-type long-acting preparations of the percutaneous absorption type.
[Patent Document 1] Japanese Patent Publication (Tokuhyo) 2004-513890
[Patent Document 2] Japanese Patent Publication (Tokuhyo) 2005-501111
[Patent Document 3] WO 2004/024155 Gazette
[Patent Document 4] Japanese Patent Publication 2006-76994
[Patent Document 5] Japanese Patent Publication 2000-44476
[Patent Document 6] WO 2003/070228 Gazette
[Patent Document 7] Japanese Patent Publication (Tokuhyo) 2004-524336